ABSTRACT
Introduction Ovarian cancer is the fifth-leading cause of cancer-related mortality in US women. There are survival disparities between non-Hispanic black (NHB) and non-Hispanic white (NHW) women. We assessed if insurance status or extent of disease modified the effect of race/ethnicity on survival for ovarian cancer. Methods A historical cohort was assembled using the 2007-2015 National Cancer Institute's Surveillance, Epidemiology, and End Result (SEER) dataset. Adult NHB and NHW (>18 years) diagnosed with regional and distant ovarian cancer were included. The outcome was five-year cause-specific mortality. Multivariable Cox regression models were fitted, including race by the extent of disease and race by insurance status interaction terms. Results For each significant interaction, separate Cox models were fitted. In total 8,043 women were included. The insurance status/race interaction was not statistically significant, but the extent of disease modified the effect of race on survival. NHB survival was lower in regional disease (adjusted hazard ratio (HR) =1.6; 95% confidence interval (CI) 1.1-2.4), while there was no difference in survival between women with distant disease (adjusted HR =1.0; 95%CI 0.9-1.2). Conclusions Ovarian cancer mortality is similar between NHB and NHW women with the distant disease but higher in NHB women with regional disease. Further research should clarify whether this difference is due to access to quality cancer treatment or other factors affecting treatment response.
ABSTRACT
Pancreatic neuroendocrine tumors (PNETs) are the second most common primary pancreatic neoplasms after pancreatic ductal adenocarcinoma. PNETs present with widely various clinical manifestation and unfavorable survival rate. The recent advances in next generation sequencing have significantly increased our understanding of the molecular landscape of PNETs and help guide the development of targeted therapies. This review intends to outline a holistic picture of the tumors by discussing current understanding of clinical presentations, up-to-date treatment strategies, novel mouse models, and molecular biology of PNETs. Furthermore, we will provide insight into the future development of more effective targeted therapies that are necessary to manage PNETs.
ABSTRACT
The receptor for hyaluronic acid-mediated motility (RHAMM) is upregulated in various cancers. We previously screened genes upregulated in human hepatocellular carcinomas for their metastatic function in a mouse model of pancreatic neuroendocrine tumor (PNET) and identified that human RHAMMB promoted liver metastasis. It was unknown whether RHAMMB is upregulated in pancreatic cancer or contributes to its progression. In this study, we found that RHAMM protein was frequently upregulated in human PNETs. We investigated alternative splicing isoforms, RHAMMA and RHAMMB, by RNA-Seq analysis of primary PNETs and liver metastases. RHAMMB, but not RHAMMA, was significantly upregulated in liver metastases. RHAMMB was crucial for in vivo metastatic capacity of mouse and human PNETs. RHAMMA, carrying an extra 15-amino acid-stretch, did not promote metastasis in spontaneous and experimental metastasis mouse models. Moreover, RHAMMB was substantially higher than RHAMMA in pancreatic ductal adenocarcinoma (PDAC). RHAMMB, but not RHAMMA, correlated with both higher EGFR expression and poorer survival of PDAC patients. Knockdown of EGFR abolished RHAMMB-driven PNET metastasis. Altogether, our findings suggest a clinically relevant function of RHAMMB, but not RHAMMA, in promoting PNET metastasis in part through EGFR signaling. RHAMMB can thus serve as a prognostic factor for pancreatic cancer.
